"Efficacy, safety and certainty of evidence for selective D1/D5 dopamine receptor partial agonists in Parkinson's disease: a systematic review, meta-analysis and GRADE assessment"
Abstract
Background: Selective D1/D5 dopamine receptor partial agonists are proposed to provide motor benefit without the impulse control disorders and somnolence associated with D2/D3 dopamine agonists. With tavapadon under regulatory review, no quantitative synthesis of this drug class exists.
Methods: Embase, MEDLINE, PubMed, Scopus and ClinicalTrials.gov were searched from inception to 31 May 2026 for randomised, double-blind, placebo-controlled trials of selective D1/D5 partial agonists in Parkinson's disease (PROSPERO CRD420261347585). Random-effects models (REML) were used. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE.
Results: Seven trials (1,540 participants) were included; five entered quantitative synthesis. In early-stage monotherapy, tavapadon improved the combined MDS-UPDRS Parts II and III score by 10.55 points versus placebo (95% CI - 13.11 to - 7.99; two trials). In levodopa-treated patients with motor fluctuations, good ON-time increased by 1.09 h per day (0.57 to 1.61; two trials). Adverse events (RR 1.36, 1.09 to 1.71), nausea (6.38, 3.23 to 12.59), dizziness (3.03, 2.15 to 4.27) and discontinuation due to adverse events (2.72, 1.07 to 6.96) were more frequent with tavapadon. Serious adverse events were not increased (Peto OR 1.13, 0.69 to 1.85). Impulse control disorder (RR 2.02, 0.51 to 8.00; nine events, one trial) and somnolence (1.20, 0.37 to 3.92) were rated at very low certainty. No outcome reached high certainty.
Conclusion:…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,540 participants or records.
Read the paper
Related studies
- Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
- Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta‐analysis, and network meta‐analysis of randomized trials with 94,283 participants
- Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis
- Exposure to WHO AWaRe antibiotics and isolation of multi-drug resistant bacteria: a systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.